Imaging the pancreatic islets in a non-invasive manner has important applications in the type-1 diabetes field. For human studies, visualization of the leukocyte infiltrate or of beta cell mass/activity may permit significant improvements in difficult-diagnoses, sequential monitoring of disease progression, and the evaluation of immunomodulatory interventions. Perhaps most important, it may allow early detection of autoimmune attack in genetically at-risk individuals, when immunointervention is likely to be the most beneficial, or signal impending conversion of anti-islet antibody positivity to overt diabetes. For murine experiments, such visualization may permit one to capture the earliest pathological events and to follow the unfolding of disease in individual animals, crucial for identifying early indicators of precise disease outcome. The overall goal of this proposed project is to exploit novel imaging methodologies developed under Project 1 to answer important questions currently being asked about type-1 diabetes in murine models. Specifically, we will: Visualize pancreatic islet inflammation, initially through magnetic resonance imaging of the microvasculature in order to examine how various genetic elements impinge on disease progression; Monitor beta-cellmass/activity via bioluminescence imaging to provide an indication of the kinetics and extent of beta-cell loss as disease unfolds.; Follow regulatory T cells by means of bioluminescence and magnetic resonance "tracking" to better understand their migration patterns and population dynamics. Results from these experiments should engender novel insights into important disease processes in type-1 diabetes mouse models, which hopefully can also be extrapolated to the human context, and should provide a basis for deciding which imaging methodologies can best be applied to human type-1 diabetes patients.